Genetic Variant XG:p.Asn132Ser (chrX-2806722-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001141919.2(XG):c.395A>G(p.Asn132Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000401 in 1,147,777 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.000042 ( 0 hom. 21 hem. )

Consequence

XG
NM_001141919.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227

Publications

0 publications found

Variant links:

Genes affected

XG (HGNC:12806): (Xg glycoprotein (Xg blood group)) This gene encodes the XG blood group antigen, and is located at the pseudoautosomal boundary on the short (p) arm of chromosome X. The three 5' exons reside in the pseudoautosomal region and the remaining exons within the X-specific end. A truncated copy of this gene is found on the Y chromosome at the pseudoautosomal boundary. It is transcribed, but not expected to make a Y-chromosome specific gene product. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

XG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.068584174).

BS2

High Hemizygotes in GnomAd4 at 2 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141919.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XG	NM_001141919.2	MANE Select	c.395A>G	p.Asn132Ser	missense	Exon 8 of 11	NP_001135391.1	P55808-3
XG	NM_001141920.2		c.377-1463A>G		intron	N/A	NP_001135392.1	P55808-2
XG	NM_175569.3		c.374-1463A>G		intron	N/A	NP_780778.1	P55808-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
XG	ENST00000644266.2	MANE Select	c.395A>G	p.Asn132Ser	missense	Exon 8 of 11	ENSP00000494087.1	P55808-3
XG	ENST00000419513.7	TSL:1	c.329A>G	p.Asn110Ser	missense	Exon 6 of 9	ENSP00000411004.3	A0A2U3U020
XG	ENST00000381174.10	TSL:1	c.374-1463A>G		intron	N/A	ENSP00000370566.5	P55808-1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112237

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000735

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000107

AC:

AN:

102921

AF XY:

0.000200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000415

AC:

AN:

1035486

Hom.:

Cov.:

AF XY:

0.0000635

AC XY:

AN XY:

330468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24358

American (AMR)

AF:

0.00

AC:

AN:

25971

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18361

East Asian (EAS)

AF:

0.00

AC:

AN:

26628

South Asian (SAS)

AF:

0.000753

AC:

AN:

47791

European-Finnish (FIN)

AF:

0.0000265

AC:

AN:

37695

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4033

European-Non Finnish (NFE)

AF:

0.00000124

AC:

AN:

806850

Other (OTH)

AF:

0.000114

AC:

AN:

43799

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112291

Hom.:

Cov.:

AF XY:

0.0000580

AC XY:

AN XY:

34465

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30968

American (AMR)

AF:

0.00

AC:

AN:

10593

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3575

South Asian (SAS)

AF:

0.000737

AC:

AN:

2713

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53198

Other (OTH)

AF:

0.00

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000155

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.20

(source)

DANN

Benign

0.20

FATHMM_MKL

Benign

0.0038

LIST_S2

Benign

0.52

M_CAP

Benign

0.0018

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

PhyloP100

-0.23

PrimateAI

Benign

0.28

REVEL

Benign

0.029

Polyphen

0.034

MutPred

0.30

Gain of phosphorylation at N132 (P = 0.017)

MVP

0.15

MPC

0.095

ClinPred

0.025

GERP RS

0.71

gMVP

0.089

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over